Glucose-induced membrane electrical activity of pancreatic B-cells mediates calcium uptake used for insulin release. The electrical response occurs in two glucose-dependent phases: as glucose level increases from zero to the threshold for insulin release, there is a subthreshold depolarization of the B-cell membrane. Additional glucose triggers both insulin release and electricalactivity. The electrical activity consists of calcium spikes superimposed on slower, periodic plateau depolarizations. As glucose level increases, the amplitudes of spikes and plateaus do not change, yet a pacemaker mechanism prolongs the plateau phases. The corresponding increase of calcium spike activity appears to mediate glucose-dependent calcium uptake. Our long term goals are to identify and charactrize the ionic mechanisms underlying the response, and to determine how they are controlled by glucose and its metabolism. Our working hypothesis proposes membrane ionic conductance mechanisms which may contribute to each of the four coupled electrical events noted above. To test this, we will use patch-clamp methods to study membrane currents through ATP-inhibited and calcium-activated potassium chanels as well as through a new voltage-dependent potassium channel, and to characterize inward currents through sodium and calcium channels.